Diseases which affect inner ear fluids, such as Meniere's disease and perilymph fistula, are not adequately understood. This is a result of our limited knowledge regarding the homeostatic mechanisms which maintain cochlear fluids in the normal ear. Over the past 5 years we have pioneered the use of ionic tracer techniques which have allowed us to characterize some of the fundamental properties of cochlear fluids. Longitudinal flow in the cochlea and communication between compartments has been monitored using a variety of techniques which involve ion-selective microelectrodes. Such electrodes can be sealed into the cochlea, permitting measurements to be made while avoiding artifacts which have been common in such studies in the past. Data have been interpreted quantitatively with the aid of mathematical models, enabling the passive solute movements to be incorporated into a generalized model of the cochlea. The same tracer techniques have now been extended, allowing us to measure endolymph volume in vivo during experimental treatments. This measure is essential if we are to investigate endolymph volume regulation in the normal ear and the mechanisms underlying hydrops. We plan to correlate physiological and biochemical changes with in vivo and histologically measures volume changes during the development of hydrops in guinea pigs. The chronology of events will be established to distinguish primary events from secondary effects. The role that endolymph calcium disturbances play in hydrops will be identified. We will also test the hypothesis that distension of Reissner's membrane impairs the normal cross-communication between scala vestibuli and scala tympani. This problem could account for the vestibular symptoms associated with Meniere's disease. These studies will be performed as part of a comprehensive investigation of cochlear fluid interactions. Experiments will be designed and interpreted in conjunction with a comprehensive kinetic model of the cochlea and related fluids. Only by understanding how the entire cochleo-vestibular system responds to pathologic disturbances can rational strategies for the prevention diagnosis, and treatment of Meniere's disease be achieved.